Our long-term objective is to understand how genes control the morphological specialization of body segments in Drosophila. Much of the work proposed in application focuses on Abdominal-B (Abd-B), a member of the bithorax complex of homeotic genes that functions to define the identities of the fifth through ninth abdominal segments. Recently, we showed that the iab-5, iab-6, and iab-7 regulatory domains of the complex are able to regulate Abd-B in trans in a proximity-dependent fashion. This interaction requires the presence of a specific region between iab-7 and Abd-B called the transvection mediation region (tmr). A major objective is to characterize the tmr more fully. We propose to use P-element mediated transformation of cosmid constructs to map the tmr with greater precision, to determine whether the tmr is required for cis, as well as trans, interactions of the iab regions and Abd-B, and to test two potential mechanisms by which the tmr might function. We also propose to test whether a specific "responder" site at Abd-B is required to mediate interactions in trans. Finally, we propose mutant screens using specially designed acrocentric FRT chromosomes to identify genes required for the trans interaction. A second major goal is to understand how the protein encoded by the pair- rule gene fushi tarazu (ftz), a key regulator of the homeotic genes, functions during segmentation. Recent results indicate that most or all of the segmentation functions of ftz do not require the DNA-binding domain (the homeodomain) of the ftz protein, and hence likely depend on protein- protein interactions. To characterize these interactions, we propose to continue analysis of cDNA clones isolated by screening an expression library using labeled ftz protein as probe. We also plan mutant screens to identify genes that interact with ftz. Finally, we propose to continue molecular characterization of the homeotic gene spineless-aristapedia (ss). Our specific aims include identification of ss trans regulators, dissection of the ss regulatory regions, and identification of ss protein dimerization partners. We also propose to map functional domains within the ss protein by characterization of a large number of mutant alleles. The health significance of the proposed research is that it may lead to better understand of how homeotic genes are regulated in humans, and hence how certain congenital abnormalities arise. In addition, the close similarity of the ss protein to the human aryl hydrocarbon (dioxin) receptor, suggests that work on ss may provide insights into the mechanisms by which aryl hydrocarbon pollutants exert toxicity in humans.